The aim of this project is to investigate macrophage-mediated cytotoxicity in patients with malignancies in order to define how macrophage cytotoxic function is altered in these patients. The macrophages from breast and gynecologic cancer patients generally did not acquire enhanced cytotoxicity for human tumor cells after incubation with LPS. However, when the macrophages isolated from colon and hematological cancer patients were studied, more than 50% of these patients possessed cytotoxic macrophages. Furthermore, LPS-induced macrophage-mediated cytotoxicity was also found to be inhibited by factors present in many cancer patients' serum. Furthermore, when indomethacin, a prostaglandin inhibitor, was added to the macrophage tumor cell mixture, the breast cancer patient's macrophages became capable of killing the tumor cells. These macrophage preparations demonstrated a 64% increase in the secretion of PGE2 when compared with macrophages obtained from normal donors. The macrophages obtained from both cancer and normal donors were found to secrete products which were cytotoxic to malignant but not normal cells. These macrophage products are strongly adsorbable to cellulose nitrate membrane filter materials, are elutable with dilute HCl, are relatively stable over a wide range of temperatures and are nondialyzable. When subjected to polyacrylamide gel electrophoresis, the tumoricidal products secreted by the macrophages obtained from cancer and normal donors could be resolved into 8-10 protein bands which were qualitatively identical.